Many theories in population genetics assume that the Mendelian ratio, 1:1, is a general rule in many organisms in natural populations. The present project attempts to challenge this basic assumption -- I propose a hypothesis that the Mendelian ratio is rather an exception; non-Mendelian ratio is the general rule in heredity. By making use of the well-studied genetic systems of Segregation Distorter (SD) and Male recombination-Mutator (MR) in Drosophila melanogaster, it is attempted to identify and establish the formal genetic basis of the elements causing distorted segregation ratio and the genetic basis of the elements modifying it. This project will cover not only one particular chromosome pair but the other chromosomes as well. A special emphasis will be placed to investigate the modes of interactions in segregation ratio among elements located on different chromosomes so that the mechanism regulating segregation frequencies of chromosomes can be understood on the entire genome basis. Some other related phenomena such as hybrid dysgenesis will also be studied. Results of these studies will require us to re-evaluate many population genetics predictions on human populations such as genetic damages due to exposure to irradiation and chemicals through generations.